Implementations described herein relate generally to devices, systems and methods enabling targeted plating of materials in high-throughput culture plates, and, more particularly, to culture well plates and lids configured to facilitate targeted placement of materials into an individual culture well.
In vitro electrophysiology culture systems having biosensors, such as microelectrode arrays (MEAs), can provide important insights into networks of electrically active cells. MEA-based electrophysiology culture systems can be configured to concurrently monitor single-cell and network-level activity over extended periods of time and without affecting the cell culture under investigation. Since their instrumental role in the landmark discovery of spontaneous waves in a developing retina, the variety and scope of MEA-based electrophysiology applications has dramatically expanded. Recently, for example, MEA-based electrophysiology culture systems have been used to investigate the suppression of epileptic activity and in the study of novel plasticity mechanisms in cultured neural networks. Advances in cell culture preparations have similarly led to applications for MEA-based electrophysiology culture systems in the fields of drug screening, safety pharmacology, and biosensing.
Present day MEA-based electrophysiology culture systems are typically designed around small-footprint, single-well devices. However, the complete analysis of complex cellular systems and processes can require repeated experiments. The number of experiments can increase quickly when considering multiple variables, such as, for example and without limitation, stimulus size, compound type, dosage strength and the like. Thus, the small-scale format of traditional MEA systems presents a “large N” problem (i.e., problems due to excessive experimental and statistical sampling sizes), whereby the serial nature of these devices can render even basic investigations time and cost prohibitive. As one illustrative example, a researcher examining the effect of pythrethroids on two-hour spontaneous activity recordings can require 8 doses of permethrin, with an N of 6 for each dose. With traditional MEA-based electrophysiology culture systems, this very simple experiment can require over $5,000 in MEA-based electrophysiology culture plates (or “MEA culture plates”) and 50 to 60 man-hours. The time investment can further increase with the logistics of culturing, maintaining, and testing dozens of individual specimen.
The applicant has developed high-throughput MEA culture plates in an ANSI/SLAS compliant format to achieve industry compliance with other high-throughput instrumentation such as robotic handlers and plate readers. Such MEA culture plates are described in U.S. Provisional Patent No. 61/899,970, filed on Nov. 5, 2013, entitled “Devices, Systems and Methods for Targeted Plating Of Materials In High-Throughput Culture Plates,” which is hereby incorporated by reference in its entirety. Such high-throughput culture plates can have well counts of, for example and without limitation, 12, 24, 48, 96, 192, 384 or 768. Further, each well plate can have an area of interest, e.g. an electroactive area that can be, for example and without limitation, about 1.25 mm to 2 mm in diameter.